Format

Send to

Choose Destination
Cancer Discov. 2017 May;7(5):462-477. doi: 10.1158/2159-8290.CD-16-1154. Epub 2017 Mar 22.

Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.

Author information

1
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
2
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
3
Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
4
Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
5
Center for Integrative Biology, University of Trento, Trento, Italy.
6
Cure First and SEngine Precision Medicine, Seattle, Washington.
7
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.
8
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, New York.
9
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
10
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
11
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York. rubinma@med.cornell.edu.

Abstract

Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high-throughput drug screening to discover effective treatment strategies. Analysis of tumor-derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3-D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted.Significance: Integration of genomic data with drug screening from personalized in vitro and in vivo cancer models guides precision cancer care and fuels next-generation research. Cancer Discov; 7(5); 462-77. ©2017 AACR.See related commentary by Picco and Garnett, p. 456This article is highlighted in the In This Issue feature, p. 443.

PMID:
28331002
PMCID:
PMC5413423
DOI:
10.1158/2159-8290.CD-16-1154
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center